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Immediate early gene induction after neonatal hypoxia-ischemia
R M Gubits1, R E Burke, G Casey-McIntosh
1Department of Neurology, University College of Physicians and Surgeons, New York, NY 10032.
Brain Research. Molecular Brain Research
|May 1, 1993
Summary
The immature brain rapidly responds to hypoxia-ischemia (H-I) by increasing immediate early gene (IEG) expression. This study shows H-I triggers multiple rapid gene response systems in developing brain cells.
Area of Science:
- Neuroscience
- Molecular Biology
- Developmental Biology
Background:
- Immediate early genes (IEGs) like FOS and JUN are crucial for cellular transcriptional responses to environmental stimuli.
- The role of IEGs in the immature brain's response to hypoxia-ischemia (H-I) remains largely unexplored.
Purpose of the Study:
- To investigate the involvement of IEG products in the immature brain's response to H-I.
- To characterize the temporal and regional gene expression patterns following H-I in developing rat brains.
Main Methods:
- Seven-day-old rat pups underwent unilateral common carotid artery ligation followed by 3 hours of hypoxia.
- RNA analysis using Northern blot hybridization was performed on various brain regions at time points from 1 to 24 hours post-H-I.
- Concentrations of nine IEG mRNAs, heat shock protein 70 (Hsp70) mRNA, and glial fibrillary acidic protein (GFAP) mRNA were quantified.
Main Results:
- Significant induction of seven out of nine IEGs (excluding TIS7 and TIS10) was observed in the ipsilateral forebrain within 1-3 hours post-H-I, with some detected up to 24 hours.
- Co-induction of multiple IEGs was a common finding in the same RNA samples.
- Hsp70 mRNA induction was localized to the ipsilateral forebrain, correlating with IEG induction, while GFAP mRNA induction occurred later (18-24 hours) in the ipsilateral forebrain.
Conclusions:
- The immature brain exhibits a robust and rapid gene expression response to H-I.
- At least three distinct rapid response systems, including IEGs, heat shock, and astrocytic responses, are activated following H-I in the developing brain.
- IEG induction appears closely linked to the initial response to H-I, while Hsp70 and GFAP induction may relate to subsequent damage and reactive processes.